provide fast relief during off periods, that could make them valuable. Inbrija is a puff of levodopa delivered through an inhaler. APL-130277 is a film placed under the tongue that dissolves and delivers apomorphine. Both therapies have shown, in clinical trials, an ability to improve patients’ motor function, compared to placebo, 30 minutes after they are taken.
“That’s a good sign that these drugs could get people out of an acute or significant off state and may give their standing medications time to work,” says Ritesh Ramdhani, a neurology professor at NYU Langone’s Fresco Institute for Parkinson’s and Movement Disorders.
So far the two experimental drugs haven’t led to any significant side effects, though they also haven’t yet been tested in multi-year studies. Acorda presented safety data from an open-label extension study at AAN yesterday. The most common side effects seen in 271 patients on Inbrija for 12 months were cough, dyskinesia (involuntary movement), throat irritation, and discolored sputum, but Acorda said most cases were mild. In total, 24 patients (8.9 percent) on Inbrija for a year stopped treatment due to side effects. Lung function didn’t decline notably more in patients on Inbrija than those on placebo, Acorda said.
“It was remarkably well tolerated from a respiratory standpoint,” says lead investigator Stuart Isaacson, a neurologist at the Parkinson’s Disease & Movement Disorder Center of Boca Raton. “The study didn’t show any compromise in respiratory function in any way, and the coughing was not a major issue at all.”
The stakes are high for Acorda. The company bullishly predicted earlier this year that the U.S. market for Inbrija alone could be worth more than $800 million. But Acorda has suffered several clinical setbacks over the past few years and was reported in January to have put itself up for sale. The last patent protecting its flagship drug, dalfampridine (Ampyra), expires in July. Inbrija, acquired via Acorda’s 2014 buyout of Civitas Therapeutics, is its best chance to keep its footing.
Experts say who they’ll prescribe Inbrija to will depend on each patient’s specific condition. As Spindler says, clinical trials are often very selective and aren’t representative of who will actually get a medicine. In the long-term study Acorda reported on at AAN yesterday, for instance, patients had to be able to use an inhaler both when their levodopa medications were working, and when they weren’t. In the real world, says Spindler, will Parkinson’s patients, whose dexterity is often compromised, have trouble using an inhaler when their symptoms hit? Will people with lung problems be able to use the inhaler? Experts also wonder if the inhaled drug will worsen lung function over several years, and whether its benefits will hold up as the disease progresses.
Acorda executive vice president of corporate communications Tierney Saccavino notes that patients in the company’s pivotal trial were directed to take Inbrija at the first sign of an off episode, not later. “We do not view this as a traditional ‘rescue therapy,” she says, adding that a wide range of Parkinson’s patients on optimized oral medication regimens were included.
Sunovion executive medical director David Blum, meanwhile, believes patients will “appreciate the ability to take their medication by putting the thin strip under their tongue,” particularly when symptoms arise. He adds that the company has tested a wide range of doses up to five times per day, which could help doctors find a “precise dose for individualized treatment.”
But experts still have questions about the Sunovion drug. Someone who freezes up, for instance, might still need help taking the sublingual film, Kompoliti says. But she also wonders whether problems like impulse control disorders—hypersexuality, overeating and other symptoms associated with dopamine agonists such as apomorphine—will crop up with long-term use. All things being equal, Dolhun says, “typically doctors would say that levodopa is a little bit more of a beneficial medication” compared to apomorphine. That is particularly the case for frail and older patients, Kompoliti says.
Ultimately, however, how widely the Acorda and Sunovion drugs are used may depend on how fast they kick in—the key question every expert Xconomy interviewed had. While the main goal for the pivotal studies of Inbrija and APL-130277 was how people felt 30 minutes after treatment, experts say the real tests will be what their patients tell them.
“It will be interesting to see in clinical practice if patients feel that [these drugs] work faster than oral medications and are beneficial enough that patients use them instead of their oral medication when they freeze,” Spindler says.
